Genetic fingerprint of aggressive colon tumours

1.organoides_tumorales_de_pacientes

Patient-derived tumour organoids (mini colon tumours). In blue: cellular nuclei; in red: cellular membranes (Image: Alexandre Calon, IRB Barcelona).

Researchers at the IRB in Barcelona have found a signature of 4-6 genes able to predict the aggressivity of colon tumours, by analysing the tissue surrounding the tumour cells.

The scientists are currently developing a test that enables the identification of patients at risk of relapse after surgical removal of the tumour by measuring these found genes. They also propose to test in patients a particular drug that blocks the metastatic capacity of colorectal cancers in mice. This drug has been already tested using organoids derived from patients’ samples.

Source:

On a more funny note, have a look at the video done this last summer by researchers at the IRB Barcelona!

Any exciting research (or videos!) done over at your laboratory or institute?

We would like to know!

Unraveling the protective role of the stroma

Research performed by David García-Molleví and his team at ICO (Barcelona, Spain), in cooperation with tebu-11018152_928445027176257_6580852836315207360_nbio laboratories, is being presented at the AACR congress in Philadelphia these days.

The poster describes how cytokine profiling of drug-disrupted tumour cell / fibroblast crosstalk provides insights to understand the protective role of the stroma. Briefly, an array including 174 cytokines was performed on tumour cell / fibroblast co-cultures. Results determine that IL1b and TGFb1 secreted by tumor cells trigger the activation of normal colonic fibroblasts (NCF) to become CAFs. The role of IL1b is not as well known as TGFb1 in a cancer context.

Cytokine arrays were used in order to determine:

i) cytokine profiling of IL1b-treated NCF
ii) profiling of tumor cell-NCF cocultures in the presence of inhibitors of IL1b and TGFb1 signaling, main triggers of NCFactivation.

This poster shows how cytokine profiling can be useful as a complementary approach for microenvironment studies in assessing reciprocal activation of tumour cells and stroma, mediators of such interplay, treatment effectiveness and new target interventions.

Would you like to have a copy of this poster? Contact us!

PGE2 role in carcinoma chemoresistance via CSC repopulation

The involvement of Prostaglandin E2 (PGE2) in cancer development has already been described (see the post “Tumour microenvironment – the dark side of PGE2). Recently, Kurtova et al. confirmed this idea by describing the role of COXII/PGE2 signalling pathway during bladder cancer cytotoxic chemoresistance. (1)

[Read more…]

Exosomes as a trigger for signaling

Extracellular vesicles in general, or exosomes in particular, are becoming a hot topic for research, especially in cancer. They seem to have different roles in tumour progression or can be used as targets to develop new therapies. In our series of posts on exosomes, we will focus today on their role in signal transduction.

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Release of microvesicles and exosomes (taken from Ref. 2).

Knowledge of the content of exosomes, and their role to in cell-to-cell communication by mediation of signal transduction, is of interest on two sides. [Read more…]

Tumour microenvironment – ameloblastomas

Following our post on tumour microenvironment and glioblastoma, we will focus today on ameloblastomas.

Ameloblastomas are benign tumours that occur in the jawbone, and invade bone. This type of tumour is treated by surgery and can cause various problems, including changes in facial countenance and mastication disorders.1-s2.0-S0006291X14X00355-cov150h

Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Cell-to-cell interactions in ameloblastoma have not been fully investigated yet. A recent publication by Fuchigami et al.  has investigated the soluble factors (i.e. secretome) involved in the formation and progression of ameloblastoma.

Using the Q-plex technology in a human ameloblastoma cell line (AM-3), as well as human fibroblasts (HFF-2) and primary-culture fibroblasts from human ameloblastoma tissues, they analysed the effect of ameloblastoma-associated cell-to-cell communications. Q-plex was used to study the cytokine secretion, namely IL-1alpha, IL-6, IL-8. Fuchigami et al. conclude that ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a tumour microenvironment (TME) that leads to the extension of this type of tumours.

32_Q_Plex__multiplex_ELISA_by_QuansysWould you like to know more about the Q-plex technology? We recently organised a webinar on this technology. Contact us if you want to receive a link with the recorded version or the PDF with the presentation!

 

Tumour microenvironment – the kinome (II)

In a previous post, we discussed  kinome studies in the tumour microenvironment (TME). We described some solutions to study known markers, but we did not look at those cases in which the biomarkers associated to the kinome are unkown, and therefore some exploration is needed. [Read more…]

Tumour microenvironment and kinome studies

We all react to external factors, even the most cold-blooded person. We might hide our emotions, but there they are.

The same happens in cancer. Cells (both the tumour cells and the normal ones) react to the environment in one direction or another. In this post, we will see how “kinome” analysis might help Researchers in better understanding cellular interactions in tumour microenvironment (TME).

[Read more…]

Tumour microenvironment – exosomes

Following our series of posts on the tumour microenvironment (TME), we will put our spotlight today on exosomes.

TME-exosomes

Proposed immunological functions of tumour-derived exosomes. Taken from Ref. 3

TME is composed on myofibroblasts, extracellular matrix and many other cell types. The tumour communicates with its microenvironment through cytokines, growth factors, chemokines, miRNAs, etc, as previously seen. Exosomes are nanosized extracellular vesicles (EVs) that allow communication between cells. They seem to play a role in the progression of some cancers (e.g. prostate cancer, glioblastoma), as well as in resistance to cancer therapies (1, 2). In fact, they modulate the immune response, explaining their role in either fighting the tumour or helping the tumour cells evade the immune system (3). [Read more…]

Tumour microenvironment and miRNA biomarkers

In previous posts, we have seen the role of inflammation and glycosylation in the tumour microenvironment (TME). All these are mainly factors at the protein level causing the tumour cells to evade the immune system and metastasise. But what about other factors?

One of the areas that has raised quite some interest recently are microRNAs (miRNAs). If you’d like to brush up your knowledge on miRNAs, you might be interested in this post by my colleague Paola Vecino. miRNAs are becoming trendy, as they seem to be involved in several disease mechanisms (not only in cancer, but also in some other pathologies, including some inflammatory diseases), and they can be used as diagnostic and/or prognostic biomarkers.

[Read more…]

NKT-cells ligands enhance oral cancer vaccine efficiency

Current cancer vaccine strategies strive to efficiently deliver in situ immunogenic Tumour-Associated Antigens (TAAs) into  functional Antigen-Presenting Cells (APCs).  Stimulated APCs cells then initiate anti-tumour reactions through local and complex immune interactions targeting also the tumour microenvironment.

In this context, Xu et al. have recently developed a new effective oral cancer vaccine platform presenting potent immunogenicity and anti-tumour activity with long-lasting protective memory response (1).

Alpha-Gal-Cer interactions with AP cells and its adjuvant effect

Schematic representation of the role of KRN7000 in linking innate and adaptive immunities through the interaction between dendritic cells (DCs)and NKT cells. Source: Alphagalcer.net and RIKEN RCAI.

The authors have designed optimized Salmonella-based vectors (Salmonella SPI2-encoded T3SS system) co-administrated with a Natural Killer (NKT) cells ligand (2). The delivery of heterogeneous TAAs into APCs has been proven to display enhanced anti-tumour activity through bacterial expressed TAAs-specific immune reponses.

Chemically synthesized NKT cells ligands (alpha-Galactosylceramide known as the αGalCer KRN7000) and its superior binding affinity analog 7DW8-5 were already known to enhance the immunogenicity and anti-tumour efficacy of bacterial vaccine vectors (3, 4).

Xu et al. clearly show here the potential interest of 7DW8-5 as a vaccine adjuvant in clinical tumour treatment with oral vaccines.

Sources:

  1. Xu et al. “Development of an Effective Cancer Vaccine Using Attenuated Salmonella and Type III Secretion System to Deliver Recombinant Tumor-Associated Antigens” (2014) Cancer Res Published Online First September 11, 2014. DOI:10.1158/0008-5472.CAN-14-1169.
  2. Nicol A. et al. “Comparison of clinical and immunological effects of intravenous and intradermal administration of a-galactosylceramide (KRN7000)-pulsed dendritic cells” (2011) Clin Cancer Res, 1;17(15):5140-51. DOI: 10.1158/1078-0432.CCR-10-3105.
  3. Xiong G. et al. “Novel cancer vaccine based on genes of Salmonella pathogenicity island 2” (2010) Int J Cancer,126:2622-34. DOI: 10.1002/ijc.24957.
  4. Li X. et al. “Design of a potent CD1d-binding NKT cell ligand as a vaccine adjuvant” (2010) Proc Natl Acad Sci U S A 2010;107:13010-5. DOI: 10.1073/pnas.1006662107.